Spectrum of Asthma in Children—III,Psychological and Social Components

Behavioural disturbances in the child, the mother-child and family relationships, and the family social structure were studied in a representative sample of the whole range of asthmatic children and compared with a control group of normal children. Behavioural disturbances occurred more often and at a statistically significant level only in the small group of children with severe and continuing asthma. These children were those with severe chronic airways obstruction as assessed physiologically and also with the most severe allergic manifestations.Predominant in the mother-child relations was an over-concern to protect the child''s health in those children with continuing asthma at 14 years of age. The families of the very severely affected group of children showed evidence of more stress than other families. Socioeconomic conditions were not significantly different in any group of asthmatic children compared with the control group.     

Spectrum of Asthma in Children—I,Clinical and Physiological Components

A sample of 315 asthmatic children, representative of the whole range of asthma in childhood, and a control group of 82 children were studied clinically and physiologically from 7 to 14 years of age. The asthmatic children were arbitrarily classified into four grades according to the relative frequency and persistence of their asthma to 14 years of age. Each of these grades could be more clearly defined on analysis of other clinical and physiological characteristics.The characteristics of severe persistent asthma were: onset usually in the first three years of life, a high frequency of attacks in the initial year, clinical and physiological evidence of persisting airways obstruction and pulmonary hyperinflation, chest deformity, and impairment of growth. By contrast, mild asthma usually began later in childhood, was episodic, and there was little or no evidence of airways obstruction between attacks. The attacks generally stopped before 10 years of age. In between these two extremes were two intermediate grades.The clinical and physiological characteristics of each grade of asthma at 14 years of age were usually evident by 10 years, and in the most severe grade by 7 years of age. These characteristics provide a sound basis for assessment, management, and prognosis.     

FcγRIIb Inhibits Allergic Lung Inflammation in a Murine Model of Allergic Asthma

Allergic asthma is characterized by airway eosinophilia, increased mucin production and allergen-specific IgE. Fc gamma receptor IIb (FcγRIIb), an inhibitory IgG receptor, has recently emerged as a negative regulator of allergic diseases like anaphylaxis and allergic rhinitis. However, no studies to date have evaluated its role in allergic asthma. Our main objective was to study the role of FcγRIIb in allergic lung inflammation. We used a murine model of allergic airway inflammation. Inflammation was quantified by BAL inflammatory cells and airway mucin production. FcγRIIb expression was measured by qPCR and flow cytometry and the cytokines were quantified by ELISA. Compared to wild type animals, FcγRIIb deficient mice mount a vigorous allergic lung inflammation characterized by increased bronchoalveolar lavage fluid cellularity, eosinophilia and mucin content upon ragweed extract (RWE) challenge. RWE challenge in sensitized mice upregulated FcγRIIb in the lungs. Disruption of IFN-γ gene abrogated this upregulation. Treatment of naïve mice with the Th1-inducing agent CpG DNA increased FcγRIIb expression in the lungs. Furthermore, treatment of sensitized mice with CpG DNA prior to RWE challenge induced greater upregulation of FcγRIIb than RWE challenge alone. These observations indicated that RWE challenge upregulated FcγRIIb in the lungs by IFN-γ- and Th1-dependent mechanisms. RWE challenge upregulated FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells. FcγRIIb deficient mice also exhibited an exaggerated RWE-specific IgE response upon sensitization when compared to wild type mice. We propose that FcγRIIb physiologically regulates allergic airway inflammation by two mechanisms: 1) allergen challenge mediates upregulation of FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells by an IFN-γ dependent mechanism; and 2) by attenuating the allergen specific IgE response during sensitization. Thus, stimulating FcγRIIb may be a therapeutic strategy in allergic airway disorders.     

Allergic Complications of Meningococcal Disease II—Immunological Investigations

Immunological investigation of four patients with meningococcal meningitis who developed arthritis or cutaneous lesions showed circulating meningococcal antigen at the time of presentation in each patient. It was cleared from the circulation over the next few days. Circulating antibody was detectable in three of the four patients about a week after the onset of the illness. A marked fall in the serum C₃ level occurred in two patients at about that time. Deposits of meningococcal antigen, immunoglobulin, and C₃ were detected in the synovial fluid white cells of the two patients studied and in one of three skin biopsies examined. These findings suggest that the arthritis and cutaneous lesions of meningococcal meningitis may be due to immune complex formation.     

Can Certain Genotypes Predispose to Poor Asthma Control in Children? A Pharmacogenetic Study of 9 Candidate Genes in Children with Difficult Asthma

Objective

We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control.

Methods

A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma.

Key Results

The results indicated that LTA4H A-9188>G, TNFα G-308>A and IL-4Rα A1727>G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p<0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Rα A1199>C, IL-4Rα T1570>C and IL-4Rα A1727>G and CA haplotype of TNFα C-863>A and TNFα G-308>A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively).

Conclusions and Clinical Relevance

The study revealed multiple SNPs and haplotypes in LTA4H, TNFα and IL4-Rα genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A-9188>G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit.     

Prevention of Influenza Virus-Induced Immunopathology by TGF-β Produced during Allergic Asthma

Asthma is believed to be a risk factor for influenza infection, however little experimental evidence exists to directly demonstrate the impact of asthma on susceptibility to influenza infection. Using a mouse model, we now report that asthmatic mice are actually significantly more resistant to a lethal influenza virus challenge. Notably, the observed increased resistance was not attributable to enhanced viral clearance, but instead, was due to reduced lung inflammation. Asthmatic mice exhibited a significantly reduced cytokine storm, as well as reduced total protein levels and cytotoxicity in the airways, indicators of decreased tissue injury. Further, asthmatic mice had significantly increased levels of TGF-β1 and the heightened resistance of asthmatic mice was abrogated in the absence of TGF-β receptor II. We conclude that a transient increase in TGF-β expression following acute asthma can induce protection against influenza-induced immunopathology.     

New Type of Allergic Asthma due to IgG “Reaginic” Antibody

This study was undertaken to examine the possibility that IgE is not the only immunoglobulin responsible for immediate allergic reactions. A group of asthmatics were investigated in whom immediate allergic reactivity of the bronchi to common inhalant allergens had been confirmed by provocation tests. Their sera were fractionated and the reaginic activity of the immunoglobulin classes was studied by passive cutaneous anaphylaxis testing in monkeys. The results showed that the immediate allergic reactions were due to IgE antibodies in most patients, but there was a group with reactions due to short-term anaphylactic IgG antibodies. It was not possible to inhibit the IgG-mediated responses with disodium cromoglycate. As these two groups had clearly different serum IgE levels the estimation of IgE provided an important guide to the management of these patients.     

Patients with Asthma and Comorbid Allergic Rhinitis: Is Optimal Quality of Life Achievable in Real Life?

Objectives

Asthma trials suggest that patients reaching total disease control have an optimal Health Related Quality of Life (HRQoL). Moreover, rhinitis is present in almost 80% of asthmatics and impacts asthma control and patient HRQoL. We explored whether optimal HRQoL was reachable in a real-life setting, and evaluated the disease and patient related patterns associated to optimal HRQoL achievement.

Methods and Findings

Asthma and rhinitis HRQoL, illness perception, mood profiles, rhinitis symptoms and asthma control were assessed by means of validated tools in patients classified according to GINA and ARIA guidelines. Optimal HRQoL, identified by a Rhinasthma Global Summary (GS) score ≤20 (score ranging from 0 to 100, where 100 represents the worst possible HRQoL), was reached by 78/209 (37.32%). With the exception of age, no associations were found between clinical and demographic characteristics and optimal HRQoL achievement. Patients reaching an optimal HRQoL differed in disease perception and mood compared to those not reaching an optimal HRQoL. Asthma control was significantly associated with optimal HRQoL (χ² = 49.599; p<0.001) and well-controlled and totally controlled patients significantly differed in achieving optimal HRQoL (χ² = 7.617; p<0.006).

Conclusion

Approximately one third of the patients in our survey were found to have an optimal HRQoL. While unsatisfactory disease control was the primary reason why the remainder failed to attain optimal HRQoL, it is clear that illness perception and mood also played parts. Therefore, therapeutic plans should be directed not only toward achieving the best possible clinical control of asthma and comorbid rhinitis, but also to incorporating individualized elements according to patient-related characteristics.     

Project Head Start—An Evaluation of the Medical Components in California

Half of 1,135 children medically examined as a part of Project Head Start in California had one or more conditions that warranted referral to a physician or dentist, and only one-fifth of these were under care. In the judgment of the examining physicians, one-third of the referable medical conditions were described as “major.” Follow-up procedures were variable and not very successful.Increased local medical society participation in planning the health services for these children is recommended as an especially important step in securing care for the problems that are identified.     

Allergic Complications of Meningococcal Disease I—Clinical Aspects

Out of 717 patients with meningococcal disease 53 showed one or more of the three allergic complications: 47 (6·6%) developed arthritis, 12 (1·7%) developed cutaneous vasculitis, and 6 developed episcleritis. These complications, which were often multiple, occurred six to nine days after the beginning of the illness and three to six days after the start of successful antibiotic therapy. Those patients with severe systemic disease were prone to the complications.Histological and bacteriological study of the arthritis and vasculitis showed that these lesions were probably not due to persisting infection and suggested that they might be due to immune complex disease.     

FROZEN RAW FOODS AS SKIN-TESTING MATERIALS—Further Studies of Use in Cases of Allergic Disorders

In further studies on the use of frozen raw food as skin-testing material in patients with allergic disorders, the results of previous work were confirmed in a greater number of subjects using a larger number of foods:Tests with frozen raw foods by the scratch method induce true positive reactions of a larger size and in greater frequency than the corresponding commercial extracts by either the scratch or the intracutaneous method.Storage in the frozen state for several years does not affect the antigenic potency of the materials. The frozen preparations have caused no harmful effects in the subjects, are free from irritant properties, and are not urticariogenic.     

Ecological studies in the plankton of certain freshwater ponds of hyderabad — India II,phytoplankton —1

Summary The paper discusses the distribution and periodicity of Volvocales, Chlorococcales, Desmids, Euglenineae and phytoplankton in general occurring in three freshwater ponds. It is observed that the polluted pond harboured densest phytoplankton population comprising of Volvocales, Chlorococcales, Myxophyceae and Euglenineae. Bluegreens were particularly abundant in alkaline waters (pH 8.69) which were rich in nitrates (12.58) and dissolved oxygen (5.5). The ponds harbouring diatoms and desmids were less polluted. It is emphasized that ecological behaviour of several species does not fall in harmony with the behaviour of the taxonomic group or class of which they are members. Therefore, attention was paid to the ecology of individual species as far as possible.In their seasonal fluctuations different algal groups were apparently favoured by the ecological conditions given below.